The goal of this research is to improve our understanding of respiratory, metabolic and cardiovascular control during exercise and to elucidate the mechanisms by which diseases limit work performance. Computerized data analyses are used to yield descriptions of physiological responses to exercise and underlying mechanisms. While exercise is the principal cardiorespiratory stress in life, a full understanding of the mechanisms which drive ventilation during exercise and cause exertional dyspnea is lacking. However, evidence is accumulating in our laboratory which suggests that exercise hyperpnea is closely coupled to CO2-flow to the lung. This would imply that cardiac output and mixed venous PCO2 are important in the ventilatory response, and that the chemical controller functions to keep arterial PCO2 relatively fixed by stimulating ventilation proportional to CO2 delivery to the lung. These data also suggest that chemical control overrides other mechanisms responsive to breathing stimuli. The carotid bodies appear to be important for tight ventilatory control. We propose to test these hypotheses during: 1) onset, 2) transition to steady-state, and 3) steady-state of exercise while perturbing certain physiological factors. We are studying the effects of limiting the rate of cardiac output increase, altering the CO2 set-point, and affecting sensitivity of the carotid bodies. Responses will be studied below and above the anaerobic threshold to discern the effects of superimposed metabolic acidosis. The role of the balance between ventilatory requirement and ventilatory capacity on the symptom of dyspnea will be evaluated in patients. Additional thrusts are to study factors affecting gas exchange during exercise and metabolic responses. A single exercise test to measure anaerobic threshold, maximal O2 uptake, work efficiency and the time constant of O2 uptake kinetics has been developed and is being used to evaluate the alterations in gas exchange. Effect of O2 carrying capacity, obstructive lung disease, restrictive lung disease and coronary artery disease on gas exchange kinetics during controlled work rate exercise will be studied.